P960: EXTRAMEDULLARY MYELOMA REMAINS AN UNMET CLINICAL NEED EVEN IN THE ERA OF NOVEL AGENT. ANALYSIS OF THE SINGLE CENTER MCOHORT.
Authors: Annamaria Brioli, Franziska Braese, Olaposi Yomade, Inken Hilgendorf, Thomas Ernst, Theresa Maria Nägler, Andreas Hochhaus, Marie Von Lilienfeld-Toal
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Patients (pts) presenting with extramedullary myeloma (EMM) have a dismal outcome. EMM often presents with high-risk features and is resistant to therapy. Despite advances in multiple myeloma (MM) treatment, EMM is still an unmet clinical need, with no standard treatment defined. Aims: To assess the outcomes of EMM in a real-world population we performed a retrospective analysis on MM pts in all disease stages treated at our unit between 01/2003 and 02/2020. Methods: Statistical analysis included descriptive statistics and Cox regression. Progression free (PFS) and overall survival (OS) was calculated from first diagnosis of MM (landmark ED MM) and from the first diagnosis of EMM (landmark ED EMM). Significance was set at p<.05. Analysis was performed with SPSS Version 26. High-risk MM was defined as in Chng et al, 2014. Results: Of 663 pts (median age 64 years [yrs, IQR 56-72], 45% female), 74 (11%) developed at least one EMM during their disease history. Pts with EMM were younger (58 vs. 64 yrs, p<.001) and presented more frequently with high-risk MM (19% vs. 9%, p<.001). Thirty pts (41%) presented with paraskeletal EMM, 44 (60%) had a real extramedullary disease (EMD). Forty-one pts (55%) presented with EMM at ED of MM (primary EMM, pEMM); in 45% EMM developed at progression (secondary EMM, sEMM). Primary EMM were more frequently paraskeletal (56%), sEMM more often EMD (78%, p=.004). The two groups did not differ in terms of age or risk status. Median time to development of sEMM was 2.4 yrs (IQR 1.5-6.2 yrs) and was constant over the years: 2003-2008: 1.7 yrs, 2009-2015: 2.6 yrs, 2016-2020: 2.4 yrs. For first treatment of EMM, proteasome inhibitors and immunomodulators were the most frequently used drug classes (38% and 16%), followed by conventional chemotherapy (15%). Only 4% of pts received immunotherapy with monoclonal antibodies. Radiotherapy was administered in 42% of cases. Responses to initial therapy commenced after diagnosis of EMM were unfavorable. At least very good partial response (VGPR) was achieved in 16% of pts. A partial response was seen in 27%, 34% had stable disease and 22% progression. Poor responses were mainly due to a poor response of the EMM, with 55% of the pts showing a discrepancy between the serologic and the EMM response. PFS of EMM pts was shorter compared to pts never developing an EMM (PFS: 53 months [mo] for non-EMM vs. 28 mo for EMM, landmark ED MM, p<.001). No difference in OS was seen (OS 76 vs. 69 mo, p=.572). Pts with sEMM had worse outcomes than pts with pEMM (PFS 25 vs. 20 mo, landmark ED MM p=.039; OS 78 vs. 52 mo, landmark ED MM p=.042). Interestingly, pts with EMD had worse PFS and OS compared to patient with paraskeletal EMM only in pEMM (PFS pEMM EMD vs. paraskeletal 41 vs. 14 mo, p=.005; PFS sEMM EMD vs paraskeletal 5 vs 3 mo, p=.96 landmark ED EMM; OS pEMM EMD vs. paraskeletal 35 vs. NR mo, p=.008; OS sEMM EMD vs paraskeletal 9 vs 7 mo, p=.32).In pts with EMM, EMD was confirmed as an independent prognostic factor for a shorter PFS in the multivariate analysis but had no impact on OS. Summary/Conclusion: This real-world analysis of a large cohort of MM pts confirms that EMM, especially those developing during disease progression, is an unmet clinical need, with a PFS and an OS of less than 1 yr from the time of sEMM development. EMD has a more aggressive behavior and should be considered separately from paraskeletal EMM. As new therapies including monoclonal antibodies do not overcome the poor prognosis of these patients, future research should be aimed at finding new treatment strategies for this challenging population. Keywords: relapsed/refractory, Multiple myeloma, High risk